Peringatan Keamanan

There are no adequate and well-controlled studies of IZERVAY administration in pregnant women. The use of IZERVAY may be considered following an assessment of the risks and benefits.^L47696

The administration of avacincaptad pegol to pregnant rats and rabbits throughout the period of organogenesis resulted in no evidence of adverse effects on the fetus or pregnant female at intravenous (IV) doses 5.1 times and 3.2 times the human exposure (based on AUC) at the maximum recommended human dose (MRHD) of 2 mg once monthly, respectively.^L47696

No studies have been conducted on the carcinogenic potential of avacincaptad pegol.^L47696

Avacincaptad pegol was negative in in vitro (bacterial reverse mutation assay, chromosomal aberration in mammalian cells) and in vivo (mouse bone marrow micronucleus) assays.^L47696

Avacincaptad pegol

DB15165

biotech approved investigational

Deskripsi

Avacincaptad pegol is an RNA aptamer covalently bound to a branched polyethylene glycol (PEG) molecule. It was developed to treat an advanced form of age-related macular degeneration (AMD) called geographic atrophy (GA).^L47696 AMD is the leading cause of vision loss in developed countries for people over 50 years old, with a global estimate of 170 million individuals affected. AMD eventually progresses to bilateral and irreversible loss of vision, whether or not the patients have the non-neovascular (dry) or the neovascular (wet) form of AMD.^A260801 Although anti-VEGF therapy is available for the neovascular form of AMD, no treatment was approved for GA.^A260801

Avacincaptag pegol was approved by the FDA on August 4, 2023, under the brand name IZERVAY for the treatment of GA secondary to AMD. This approval is based on the positive results obtained from 2 phase 3 clinical trials GATHER1 and GATHER2.^L47701

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) The estimated apparent systemic half-life of avacincaptad pegol is approximately 12 days.[L47696]

Volume Distribusi Limited information is available on the volume of distribution of avacincaptad pegol

Klirens (Clearance) Limited information is available on the clearance of avacincaptad pegol

Absorpsi

Following a single dose of avacincaptad pegol, maximum avacincaptad pegol plasma concentrations (C_max) are estimated to occur approximately 7 days post-dose and mean (CV%) free avacincaptad pegol plasma Cmax is estimated to be 68.4 ng/mL (57.8%) in neovascular AMD (nAMD) patients. The AUC_{0-28 days} following a single 2 mg dose is 1064 day?ng/mL. Based on a population pharmacokinetic analysis of patients with nAMD, the predicted steady-state avacincaptad pegol Cmax is 83.9 ng/mL after monthly intravitreal administration of avacincaptad pegol 2 mg.^L47696 In humans, avacincaptad pegol plasma concentrations are predicted to be approximately 7,000-fold lower than vitreal concentrations.^L47696

Metabolisme

The metabolism of avacincaptad pegol has not been fully characterized. Avacincaptad pegol is expected to be catabolized by endonucleases and exonucleases to oligonucleotides of shorter lengths.^L47696

Rute Eliminasi

The elimination of avacincaptad pegol has not been fully characterized. Avacincaptad pegol is expected to be catabolized by endonucleases and exonucleases to oligonucleotides of shorter lengths which may be excreted renally, in a similar manner to the elimination of endogenous RNA.^L47696

Interaksi Obat

0 Data

Tidak ada data.

Target Protein

Complement C5 C5

Referensi & Sumber

Artikel (PubMed)

PMID: 15100315
Niculescu T, Weerth S, Niculescu F, Cudrici C, Rus V, Raine CS, Shin ML, Rus H: Effects of complement C5 on apoptosis in experimental autoimmune encephalomyelitis. J Immunol. 2004 May 1;172(9):5702-6. doi: 10.4049/jimmunol.172.9.5702.
PMID: 32882310
Jaffe GJ, Westby K, Csaky KG, Mones J, Pearlman JA, Patel SS, Joondeph BC, Randolph J, Masonson H, Rezaei KA: C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial. Ophthalmology. 2021 Apr;128(4):576-586. doi: 10.1016/j.ophtha.2020.08.027. Epub 2020 Sep 1.
PMID: 33741584
Cabral de Guimaraes TA, Daich Varela M, Georgiou M, Michaelides M: Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions. Br J Ophthalmol. 2022 Mar;106(3):297-304. doi: 10.1136/bjophthalmol-2020-318452. Epub 2021 Mar 19.

Link

Contoh Produk & Brand

Produk: 1 • International brands: 0

Produk

Izervay

Injection • 20 mg/1mL • Intravitreal • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.